Question 
Can I define bathymetry from a dfsu file instead of a mesh file? 

Answer 
Partly. Mesh bathymetry values can be overruled by using the Depth Correction functionality. 

Per default the Depth Correction defines the bed level change compared to the input mesh. However, the model will expect the input item to be the total water depth with respect to still water level (incl. any datum shift defined in the input file) if the input file is manually edited such that the ‘type’ parameter is set to 2 - see example in Fig. 1. The input mesh file will only be used to define the mesh resolution. 

Fig. 1 - Parameters to be modified manually in the setup file

FURTHER INFORMATION & USEFUL LINKS
MIKE 21 Flow Model FM. Hydrodynamic Module. User Guide